The Sega 32X can only be used in conjunction with a Mega Drive/Genesis system. It is inserted into the system like a standard game cartridge, although it does require its own separate power supply and a cable linking it to the Mega Drive. Without the cable to the Mega Drive, the sprite layer is invisible. Besides playing its own cartridges, it also acts as a pass through for Mega Drive games, so it can be used as a permanent attachment. The Sega Virtua Processor based Virtua Racing is the only exception - the game will not run on a Mega Drive with a 32X unit attached due to its processor (there was an enhanced version of the game, Virtua Racing Deluxe, available for the 32X, however). Also, Sega's Power Base Converter, which allows one to play Sega Master System games on a Mega Drive/Genesis, could not be used with the 32X attached. This is because the Power Base Converter uses all of the connection pins in the Mega Drive/Genesis itself, but the 32X only passes through those connections that are necessary to play games.

The 32X came with a spacer so it would fit properly with the Mega Drive II. It could be used with the Sega Multi-Mega/Sega CDX system, but the spacer would not accommodate the CDX, which created a number of user-unfriendly conditions in the unit. An additional spacer was made for this console but had to be purchased separately, according to the 32x user manual. Without the use of the spacer on a Mega Drive II, some of the 32X hardware was left exposed and vulnerable. The combined unit was also very prone to tipping over, risking damage to the unit and games. In addition to the physical problems, there was also an issue with FCC approval.

Most 32X games cannot be played unless the distribution region of the game matches the region of the console. Two games, Darxide and FIFA Soccer '96, were only released for the PAL 32X. However, FIFA 96 is one of the few games with no region protection, meaning that gamers in the USA could play an imported copy.

All but one of the games released for the Japanese market were released in the United States, albeit some had different names. The one Japanese-only game was Sangokushi IV (known as Romance of the Three Kingdoms IV).
Sega Mega-CD 32X

In addition to regular cartridge-based 32X games, there were also a very small number of CD-ROM games for the 32X. These games were labeled with Sega Mega-CD 32X (Sega CD 32X in North America). As the name suggests, these required both the 32X and Mega-CD/Sega CD addons. The lack of a significant userbase due to the high cost of purchasing all three necessary components saw only five games released, only one of those developed by Sega. [4] The most notable of these was a new version of the infamous Night Trap with 32,768 onscreen colors instead of the 64 found on the regular Mega-CD/Sega CD version.